The University of North Carolina at Chapel Hill

John Sondek

Thomas K Harden

Qisheng Zhang

Michelle E Kimple

Matthew Owen Barrett

Wei Gang Huang

Stephanie Hicks

Gary Lynn Waldo

Thomas Henry Charpentier

Rafael Rojas

The present invention provides compositions and methods for modulating G-alpha-q activity and methods of screening of test substances for the ability to modulate G-alpha-q activity.

Methods and compositions for modulating G-alpha-Q signaling

The present invention provides fluorogenic substrates and methods of use in detecting and analyzing phospholipase C isozyme (PLC) activity.

Fluorogenic sensors for phospholipase C isozymes

The present invention provides a method of identifying a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase, comprising: a) contacting the compound with a guanine nucleotide exchange factor and a GTPase and obtaining a baseline fluorescence measurement; b) contacting the guanine nucleotide exchange factor and the GTPase without the compound and obtaining a baseline fluorescence measurement; c) adding a fluorophore-conjugated GTP to the components of (a) and (b), respectively; d) obtaining fluorescence measurements of the respective components of (c) over time; e) subtracting the respective baseline fluorescence measurements of (a) and (b) from each fluorescence measurement of (d); and f) comparing the resulting fluorescence values of (e), wherein a decrease or increase in the rate of fluorescence change with the compound as compared with the rate of fluorescence change without the compound identifies a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase. Further provided are compounds of the invention and pharmaceutical compositions comprising compounds of the invention useful for the treatment of cancer and neurological disorders.

Methods for identifying chemical modulators of Ras superfamily GTPase activity

The present invention relates to methods for purifying and for detecting the presence of a protein. The invention employs a NorpA sequence and a PDZ1 domain. A protein tagged with a NorpA sequence can associate with PDZ1 domain. Similarly, a protein tagged with a PDZ1 domain can associate with a NorpA sequence. This interaction forms an aspect of the protein purification methods and protein detection methods of the present invention. Recombinant expression vectors and a protein purification solid phase are also disclosed, as well as protein detection and purification kits.

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Chapel Hill, NC, United States of America

John Sondek